The purpose of this project is to elucidate the neural mechanisms and principles of treatment of chronic pain syndromes. Current intramural clinical drug trials are focused on antagonists of glutamate, the nervous system's primary excitatory neurotransmitter. We are conducting a placebo-controlled study of the new anticonvulsant topiramate in chronic lumbar radiculopathy pain. A new program in pain genetics has localized a gene affecting pain behaviors to a small region of one chromosome containing several genes whose gene products have previously been linked to pain processing. Candidate gene studies are beginning in a cohort of 500 patients with 10-year followup of sciatica in the Maine Lumbar Spine Study. Extramural collaborations include a collaboration with Johns Hopkins in which morphine treatment was superior to tricyclic antidepressant treatment in patients with postherpetic neuralgia, the first direct comparison of these two standard treatments.